Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands.

Authors:
Dr Kovela Satish, PhD
Dr Kovela Satish, PhD
Indian Institute of Chemical Technology, Hyderabad
Synthetic and medicinal chemistry
Hyderabad, Telangana | India

Eur J Med Chem 2018 Dec 18;160:171-182. Epub 2018 Sep 18.

Department of Refractory Viral Infections, National Center for Global Health & Medicine Research Institute, Tokyo, 162-8655, Japan; Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Kumamoto, 860-8556, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.

We describe the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors with carboxamide derivatives as the P2 ligands. We have specifically designed aminothiochromane and aminotetrahydronaphthalene-based carboxamide ligands to promote hydrogen bonding and van der Waals interactions in the active site of HIV-1 protease. Inhibitors 4e and 4j have shown potent enzyme inhibitory and antiviral activity. High resolution X-ray crystal structures of 4d- and 4k-bound HIV-1 protease revealed molecular insights into the ligand-binding site interactions.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S02235234183081
Publisher Site
http://dx.doi.org/10.1016/j.ejmech.2018.09.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237192PMC
December 2018
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